Safety concerns regarding 5α reductase inhibitors for the treatment of androgenetic alopecia.

PURPOSE OF REVIEW: To examine the clinical and basic studies regarding persistent adverse effects associated with 5α reductase inhibitor treatment for androgenetic alopecia.

RECENT FINDINGS: Recent postmarketing reports and a US Food and Drug Administration analysis have documented uncommon persistent sexual and nonsexual side-effects in a subset of younger men who have taken finasteride 1 mg for androgenic alopecia. While the mechanisms of the sexual side-effects in humans is incompletely understood, one study found lower cerebrospinal fluid concentrations of dihydrotestosterone, progesterone, dihydroprogesterone and allopregnanolone, and higher levels of testosterone, 5α-androstane-3α,17β-diol and pregnenolone. Another study found up-regulation of the androgen receptor in the human foreskin with a mean of 5 years after finasteride discontinuation. Studies of erectile dysfunction in finasteride-treated rats showed fewer autophagosomes in smooth muscle on transmission electron microscopy, increased apoptosis, decreased smooth muscle, increased collagen deposition and decreased endothelial nitric oxide synthase. Finally, 5α reductase inhibitors have also been found to alter semen parameters in healthy men.

SUMMARY: Multiple animal studies provide a biological basis for many of the persistent effects seen in humans such as erectile dysfunction, depression and decreased alcohol consumption. Prescribers of 5α reductase inhibitors should discuss the potential risks with their patients seeking treatment for androgenetic alopecia.